CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 1, January–April 2023 AFRICA 39 Second transcatheter closure for residual shunt following percutaneous closure of patent foramen ovale. EuroIntervention 2017; 13(7): 858–866. 26. Dearani JA, Ugurlu BS, Danielson GK, Daly RC, McGregor CG, Mullany CJ, et al. Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events. Circulation 1999; 100(suppl_2): II-171-Ii-5. 27. Devuyst G, Bogousslavsky J, Ruchat P, Jeanrenaud X, Despland P-A, Regli F, et al. Prognosis after stroke followed by surgical closure of patent foramen ovale: a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound. Neurology 1996; 47(5): 1162–1166. 28. Ruchat P, Bogousslavsky J, Hurni M, Fischer A, Jeanrenaud X, Von Segesser L. Systematic surgical closure of patent foramen ovale in selected patients with cerebrovascular events due to paradoxical embolism. Early results of a preliminary study. Eur J Cardio-thorac Surg 1997; 11(5): 824–827. 29. Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366(11): 991–999. 30. Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013; 368(12): 1083–1091. 31. Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017; 377(11): 1022–1032. 32. Mas J-L, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017; 377(11): 1011–1021. 33. Lee PH, Song J-K, Kim JS, Heo R, Lee S, Kim D-H, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiolol 2018; 71(20): 2335–2342. 34. Søndergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017; 377(11): 1033–1042. Aspirin reduces cardiovascular events in elderly with raised Lp(a): ASPREE analysis Low-dose aspirin for the primary prevention of cardiovascular events may specifically benefit older individuals with genotypes associated with elevated plasma lipoprotein(a), outweighing harm related to major bleeding, found a new analysis of the ASPREE trial in the Journal of the American College of Cardiology. The role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention has not been established and this study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)- associated genotypes in the setting of primary prevention. The results concluded that it does. ‘Our study provides evidence that aspirin may specifically benefit older individuals with genotypes for elevated plasma Lp(a) in the setting of high-risk primary prevention of cardiovascular events and that overall benefit may outweigh harm related to major bleeding,’ said the authors, led by Paul Lacaze, Monash University, Melbourne, Australia. They added that similar observations had been previously seen in another large aspirin primary-prevention study conducted in younger women, the Women’s Health Study, and the current analysis provides validation of those findings. ‘Our results provide new evidence to support the potential use of aspirin to target individuals with elevated Lp(a) for the primary prevention of cardiovascular events,’ the researchers said, acknowledging that these results would be strengthened by the use of directly measured plasma Lp(a) levels, in addition to Lp(a) genotypes. ‘Nonetheless, given the lack of any currently approved therapies for targeting elevated Lp(a), our findings may have widespread clinical implications, adding evidence to the rationale that aspirin may be a viable option for reducing Lp(a)-mediated cardiovascular risk.’ Medscape reports that Lacaze and colleagues said elevated plasma Lp(a) levels confer up to four-fold increased risk of cardiovascular disease, with around 20 to 30% of the general population affected. Despite the high burden and prevalence of elevated plasma Lp(a), there are currently no approved pharmacological therapies targeting this lipoprotein. Although promising candidates are in development for the secondary prevention of Lp(a)-mediated cardiovascular disease, it will be many years before these candidates are assessed for primary prevention. For the current study, they analysed data from 12 815 ASPREE participants who had undergone genotyping and compared outcomes with aspirin versus placebo in those with and without genotypes associated with elevated Lp(a) levels. Results showed that individuals with elevated Lp(a)-associated genotypes, defined in two different ways, showed a reduction in ischaemic events with aspirin versus placebo, and this benefit was not outweighed by an increased bleeding risk. Specifically, in the placebo group, those who carried the rs3798220-C allele, which is known to be associated with raised Lp(a) levels, making up 3.2% of the genotyped population in the study, had an almost two-fold increased risk of major adverse cardiovascular events than those not carrying this genotype. However, the risk was attenuated in the aspirin group, with carriers of the rs3798220-C allele actually having a lower rate of cardiovascular events than non-carriers. In addition, rs3798220-C carrier status was not significantly associated with increased risk of clinically significant bleeding events in the aspirin group. Similar results were seen with the second way of identifying patients with a high risk of elevated Lp(a) levels using a 43-variant genetic risk score (LPA-GRS). In the whole study population, aspirin reduced major adverse cardiovascular events by 1.7 events per 1 000 person-years and increased clinically significant bleeding events by 1.7 events per 1 000 person-years, suggesting parity between overall benefit versus harm. However, in the rs3798220-C subgroup, aspirin reduced major adverse cardiovascular events by 11.4 events per 1 000 person-years (a more than six-fold higher magnitude of cardiovascular disease risk reduction than in the overall cohort), with a bleeding risk of 3.3 events per 1 000 person-years, the researchers report. ‘Hence in rs3798220-C carriers, aspirin appeared to have a net benefit of 8.1 events per 1 000 person-years,’ they said. continued on page 58
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